# Effect of _Tinospora cordifolia_-Derived Phtocomponents on Cancer: A Systematic Review
## 4 Discussion
### Anti-Carcinogenic Effect of Tc Phytocomponents  
In vitro studies: In the included studies, the _Tc_-extracted phytocompounds were used in combination with conventional chemotherapeutics including: fluorouracil, cisplatin, paclitaxel, suramin, doxorubicin, mitomycin, adriamycin, and methotrexate. The _Tc_ extract berberine (an alkaloid) has shown to inhibit cell cycle, differentiation, and epithelial-mesenchymal transition on HEP2 human laryngeal cancer cell lines [5]. New clerodane-furano-diiterpene-glycoside obtained as an aqueous-alcoholic extract through bioassay-guided fractionation exhibited significant cytotoxic effect and induced apoptosis in human lung carcinoma (A549), prostate (PC-3), SF-269(CNS), melanoma (MDA-MB-435), colon cancer (HCT-116) and breast cancer (MCF-7) cell lines. It was observed the induction of apoptosis was Reactive oxygen species-mediated through mitochondria by activation of the caspase pathway [6]. [PERSON] et al. identified phenolic compounds from a fungal extract of endophytic fungus _Cladosporium velox_ TN-9S isolated from the stem of _Tc_. Total phenol content was 730 ug gallic equivalents/mL as determined by Folin Ciocalteu reagent. The IC\({}_{50}\) value was less than 100 ug/mL. These phenolic compounds have shown to exhibit a mild genotype potential against DNA damage on Chinese hamster ovary cell lines after the treatment with non-ionic surfactant nonylphenol. It was also noted that the endophyte's capability to synthesize phytocomponent was similar to the host plant. Their non-mutagenic and non-cytotoxic nature was suggested to enhance the antioxidant and genoprotective potential [8]. [PERSON] et al. identified the phytocompounds from _Tc_ extracts such as N-formylannoninain, magnoflorine, jatrorrhizine palmitate, 11-hydroxymustakone, cordifolioside A, tinocordiside and yangambin through spectroscopic analysis. These phytocompounds were shown to exhibit anti-cancer properties on several human cancer cell lines including KB (human oral squamous carcinoma), CHOK-1 (hamster ovary), HT-29 (human colon cancer) and SiHa (human cervical cancer). [PERSON] et al. compared the anticancer activity for different fractions of the _Tc_ extract. It was noted that combining the phytocompounds increased the anti-carcinogenic properties through a synergistic effect [9]. The ethanol phytofraction obtained from plant samples of _Tc_ by [PERSON] et al. were cytotoxic to IMR- 32 human neuroblastoma cancer cell lines. Analysis of the cellular and nuclear morphology through immunostaining revealed Tc induced apoptosis, increased expression of senescence markers. Anti-metastatic activity in the form of a reduced cell migration capacity was also observed. Protein assays result expressed the arrest of cells in the Go/G1 phase. [PERSON] et al. extracted phytocomponents from Tc plant including anthraquinones, terpenoids, saponins and phenol. This component effectively inhibited the growth of prostate, ovary and breast cancer cell lines. _Tc_ extracts were also shown to exhibit antiproliferative, apoptotic-inducing, anti-migratory and antimetastatic potential on glioma cells. [12]. Butanoic fractions (pyrrole-based small molecules) were shown to induce apoptosis on breast cancer cells. [PERSON] et al. determined apoptotic induction by evaluation by various apoptotic markers, ROS generation, caspase activity, and cell cycle analyzing. They found phytocomponents of _Tc_ extract having anticancer activity and also observed inhibition of tumor proliferation. Despite promising results, the major limitation of most of the abovementioned studies is that several key aspects, including the complete mechanism of action, signaling, and pharmacological actions were nor clearly delineated [13]. Quercetin and rutin belong to phenolic phytocomponents extracted from Tc showed antiproliferative activity and was confirmed on human breast cancer MDA-MB-231 cells through induction of apoptosis, expression of altered genes and checking for the levels of intracellular ROS.