The several million deaths due to cancer each year indicates that the current standard of cure with its chemotherapeutic drugs is inadequate. WHO informs that the global cancer rates could increase by 50% by 2020 more than 50% and the majority to get affected will be in in low and medium income countries, with lack of chemo drugs in addition to other resources [1]. There is an urgent need for alternate anticancer drugs. Targeting protein–protein interactions (PPIs) provides opportunities for new cancer therapies. Modulating PPI interfaces with organic molecules has been found to be challenging one, and few researches have successfully resulted in the development of new clinical drugs. The unique properties exhibited by metal compounds render an attractive support for the development of bioactive leads. The enantiomeric iridium (III) metal compound could potentially be used as starting scaffolds for the development of more potent Ras/Raf PPI inhibitors for the treatment of kidney cancer [2]. Benzofuran-conjugated iridium(III) complex has been used as an anti-prostate cancer agent [3]. Prolyl-isomerase 1 (Pin1), a conserved enzyme inhibitor blocks NF-kB signalling in prostate cancer cells [4]. Rhodium(III) Complex has been to inhibit proliferation of TP53- mutated Triple-negative Breast Cancer Cells [5]. Also, we can use natural phytochemicals from plants/herbs and other natural resources to treat cancer. Phytochemicals are fully loaded with nutraceuticals that have abundant anticancer properties. Figure 1 shows an illustration of the mechanisms of action of phytochemicals to control cancer [6]. This review identifies and discusses the various phytochemical in a number of common plants/fruits that we intake.

Figure 1: Various Anti-cancer Mechanisms of Phytochemicals [6].

Findings from various laboratory studies [7] have shown that phytochemicals have the tendency to do the following actions.

1. Acts as a supplement to boost immune system

2. Helps to arrest carcinogens forming substances that we consume.

3. Helps to decrease inflammation that stimulates cancer growth.

4. Helps to stabilize unstable molecules that can trigger cancer

5. Help in hormone regulation

6. Fight against carcinogens from attacking healthy cells

7. Prompt damaged cells to self-destruct (autophagy) before reproduction.

8. Slows down the growth rate of carcinogens.

9. Helps to put a stop to DNA damage

In addition, they significantly reduce the risk of many cancers [8]:

1. Reduced incidence of neoplasia induced by chemical carcinogens

2. Preventing nitrosation of susceptible secondary amines and amides to form highly potent carcinogenic nitrosamines and nitrosamides in our foods

3. Potent chemical nucleophiles

4. Inhibitors of kinases by reducing hyper proliferation of Epithelial cells

5. Induction of carcinogen detoxification

6. Inhibition of tumor cell proliferation

7. Antimicrobial effect, Free radical scavenging (Antioxidant effect)

8. Inhibition of DNA adduct formation

9. Induction of apoptosis and cell cycle arrest

10. Modification of carcinogen and tumor metabolism

There are three major phytochemicals groups: polyphenols, terpenoids and thiols. Polyphenol group consists of flavonoids, phenolic acids and other non-flavonoid polyphenols such as tannin, curcumins, lignans. The terpenoids are classified into carotenoids and non-carotenoid terpenoids. The thiols includes the glucosinolates, allyl sulfides and non-sulphur containing indoles [9]. Antioxidant property of the phytochemicals helps to prevent cell damage from free radicals [10]. So far, several phytochemicals have been identified, and scientists have started investigating very few (Table 1) lists some of the better researched phytochemicals, their food sources and potential benefits [7].

Table 1: Classification of phytochemicals with notable food rich sources and their health benefits.

Phytochemical screening are carried out for all the extracts as per the standard methods [11-14]. To detect the alkaloids, Mayer’s test, Wagner’s test, Dragendroff’s test, and Hager’s test are conducted. For the detection of carbohydrates, Molisch’s test, Benedict’s test, and Fehling’s test are utilized. Modified Borntrager’s test, Lega’s test, and Keller-Kiliant test are used for detecting glycosides. Saponins are detected using Froth test and Foam test. Phytosterols are detected using Libermann Burchard’s test and Salkowski’s test. Ferric Chloride test is used to detect phenols, while flavonoids are detected using Alkaline Reagent test and Lead acetate test. Tannins are detected using Gelatin test and proteins and aminoacids using Xanthoproteic test and Ninhydrin test. Copper acetate test is used for detecting diterpenes.

Phytochemical studies of our previous research work on black and green grape extracts are shown in (Table 2) [15]. The extracts were prepared using both electrical pulses as well as standard methods. Here, + indicates the presence of phytochemicals, ++ indicates the presence of abundant phytochemicals, - indicates the absence of phytochemicals. The black grape extracts contained the following phytochemicals: phenol, tannin, flavonoid, saponin, anthocyanin, catechin, alkaloids, anthraquinones, carbohydrates, terpenoids, and it does not contain steroid, carotenoid. The green grape extracts contained the following phytochemicals: phenol, tannin, flavonoid, saponin, catechin, alkaloids, anthraquinones, carbohydrates, and it does not contain anthocyanin, steroid, terpenoids, carotenoid. Grape extract exhibited the biological activities such as anticancer and antioxidant activity. The antioxidant capacity of 50 μl concentration of grape extract is 78.43%. The effectiveness of the grape extract was studied against cervical cancer, using Hela Cells. Grape extract exhibited potential anticancer effect against cervical cancer cell Hela. Cytotoxicity studies revealed that, 50% inhibition concentration of grape extract is obtained as 115.05 μg/ml. Table 3 shows the phytochemical studies of our previous research work on Vinca rosea root extract. The ethanolic extracts of Vinca rosea roots indicated the presence of alkaloids, flavonoids, and terpenoids and the absence of saponin, polyphenols, steroids, and tannins [16]. Here also both electrical pulses and standard method were used to prepare the extract using ethanol. Table 4 shows the preliminary phytochemical analysis of a few selected spices [17], including Capparis spinosa (Caper’s shrub), Cinnamomum verum (Cinnamon’s stem), Illicium verum (Star anise’s bark), Allium sativum (garlic bulbs), and Curcuma longa (turmeric’s stem). From this study, it is revealed that Cinnamomum verum contains more number of biologically active constituents. The root and leaf extracts of the five plants, Baptisia tinctoria, Sivapithecus indicus, Passiflora edulis, Acacia longifolia, Solanum trilobatum are summarized in Table 5 [18]. Solanum trilobatum has indicated the presence of phytochemicals, such as alkaloids, flavonoids, glycosides, phenols, saponins, sterols, and tannins. Thus, the preliminary phytochemical screening tests helps to detect the bioactive compounds. Further steps such as purification and characterization is necessary for the development of drugs. T chloroform, methanol, and n-hexane are summarized in Table 6 [15]. The chloroform extracts exhibited the presence of few phytochemicals such as alkaloids, flavonoids, reducing sugar, saponins, tannins, and terpenoid except glycoside, anthraquinone, phlobatannin, and steroid. The methanolic extracts showed the presence of all screened phytochemicals, such as alkaloids, anthraquinone, flavonoids, glycoside, phlobatannin, reducing sugar, saponins, steroid, tannin, and saponin. n- Hexane extracts traced very few phytochemicals such as flavonoids, reducin he results of the phytochemical screening of T. stocksianum extracts by using solvents such as g sugar, saponins, tannins, and failed to detect alkaloids, anthraquinone, glycoside, phlobatannin and terpenoid [19]. In addition to fruits and plants, phytochemicals are also abundant in marine algae and seaweed. Gdelidiella acerosa (Marine red algae) showed [20] the presence of various phytochemicals. Table 7 furnishes the various phytochemicals found in this. Similarly the phytochemicals in the marine seaweed, Sargassum wightii is furnished in Table 8 [21]. Sargassum wightii were collected from the Gulf of Mannar, at the Mandapam coast, Tamil Nadu, South India. More phytochemicals are present in ethyl acetate extract of S. wightii. The abundance of phytochemicals in ethyl acetate, ethanol, and methanol extract is attributed by the mid-polar nature of the solvents. S. wightii extract prepared using non-polar solvents such as hexane, and methylene dichloride has less number of phytochemicals than the mid-polar solvent’s S. wightii extract. Their extracts were treated on lung cancer cells, A549 and found to be effective. Without notable cytotoxicity, their extracts were found to be effective in targeting PI3K or its components. Earlier studies [22-24] report that they have antioxidant, anticoagulant, anticholinesterase, antimicrobial, antifertility, antifungal, and anticancer properties. A comparison with the phytochemicals in the Rwandan plants (Table 9) indicate that similar phytochemicals are present in those too [25]. This means the drug developed using these phytochemicals could be made in other countries, which means the cost could be considerably reduced and with reduced cost and side effects using these natural phytochemicals extract, it is possible to better serve the cancer patients.

Table 2: Phytochemicals in various aqueous grape fruit extracts [15].

Table 3: Phytochemical screening of Vinca rosea root extract [16].

Table 4: Phytochemicals in a few selected spices [17].

Table 5: Phytochemicals in some selected plants [18].

Table 6: Phytochemical screening of Teucrium stocksianum using different solvents [19].

Table 7: Phytochemicals in Gelidiella acerosa [20].

Table 8: Phytochemicals in Sargassum wightii [21].

Table 9: Phytochemicals in Rwandan plants [25].

Phytochemicals from grapes, Vinca rosea, spices, marine red algae and similar other resources could be effectively used as cost effective alternative to conventional expensive medicines used for anticancer treatment. They are gentle on our bodies and have no or less side effects. Either as the pure compounds or as standardized extracts, they provide unlimited opportunities for new drug leads because of the unmatched availability of chemical diversity. The bioactivity of natural products is associated with the effects of various phytochemicals, such as tannins, terpenoids, cardiac glycosides, saponins, flavonoids among others. The extracts can be prepared using electrical pulses with over 10% increased volume. Also, they could be uploaded into the tumor using electrical pulses (electrochemotherapy [26,27]), providing a new treatment modality that could be transferable to clinical practice.