Beta sitosterol and Daucosterol (phytosterols identified in Grewia tiliaefolia) perturbs cell cycle and induces apoptotic cell death in A549 cells

Abstract

Lung cancer is the leading cause of cancer related deaths both in developed and developing countries. Since majority of the existing therapeutic methods harms both normal and malignant cells, a viable alternative is to switch into safe and beneficial traditional medicinal plants. Hence the present study was framed to identify selective anti-lung cancer agents from the medicinal plant Grewia tiliaefolia (GT). Cell viability experiments showed that benzene extract of GT (BGT) leaf effectively inhibited the growth of A549 cells, while being non-toxic to normal human lung L132 and PBMC cells. Ames and comet assays demonstrated that BGT is of non-mutagenic and non-genotoxic nature in untransformed cells. The hematological and histopathological profiles of the in vivo acute and sub-acute toxicity studies demonstrated that BGT is safe and tolerable. Importantly, western blot analysis and Annexin V-FITC staining confirmed that BGT promotes mitochondrial dependent apoptotic cell death in A549 cells by arresting cell cycle at G2/M phase. Bio-assay guided fractionation revealed the presence of phytosteols (β-sitosterol and daucosterol) which significantly inhibited the growth of A549 cells both alone and in combination. This study warrants that these phytosterols in alone or in combination can be considered as safe and potential drug candidates for lung cancer treatment.

Daucosterol from Crateva adansoniiDC (Capparaceae) reduces 7,12‐dimethylbenz(a)anthracene‐induced mammary tumors in Wistar rats

“…The same authors also reported that daucosterol had proapoptotic effects in prostate cancer cells and induced anti-metastatic effects by decreasing chemotaxis and cell migration, while increasing cell adhesion to fibronectin and collagen matrix. 20 Although several studies have demonstrated the antitumor/anticancer effects of daucosterol on human as well as animal cancer cell lines from various origins (colorectal, lung, neuronal, breast, and prostate), [20][21][22][23] no scientific evidence of its curative potential against breast cancer have been conducted yet. Therefore, the present study aimed at evaluating the potential of daucosterol from C adansonii DC to reduce breast tumors induced by the DMBA in rats.…”

“…several scientific works have focused on the valorization of natural substances that can inhibit the growth of breast cancer cells in vitro and/or prevent or abrogate mammary tumors in vivo 20,22,23. Although results obtained in vitro are good indicators of a possible anticancer activity, those obtained in vivo are more reliable because they integrate all the complexity of the actions and interactions resulting from several systems.…”

“…Daucosterol might act as its structural analogue daucosterol linoleate which was demonstrated to inhibit tumor growth and tumor weight at 100 mg/ kg in MCF-7 xenograft nude mice model, by activating the intrinsic caspase-dependent apoptosis 39. Additionally, many scientific reports have demonstrated and discussed the potential of daucosterol to trigger apoptosis through the caspase signaling pathway in various cell lines, including breast cancer cells [20][21][22][23]40. Furthermore, some authors showed that daucosterol (IC50 9.77 μg/mL) as well as daucosterol linoleate (IC 50 53.27 μg/mL) induced their cytotoxic effects in MCF-7 breast cancer cells through the intrinsic pathway of apoptosis.…”

Network Pharmacology Approach Reveals the Potential Immune Function Activation and Tumor Cell Apoptosis Promotion of Xia Qi Decoction in Lung Cancer

“…Bio-assay guided fractionation showed the presence of phytosteols (β-sitosterol) which significantly inhibited the growth of A549 cells and promoted apoptosis alone or in combination. This study ensures that these phytosterols, alone or in combination, can be considered as safe and potential drug candidates for LC treatment [41]. Kaempferol in PR can act on 13 targets of LC.…”

In vitro Antiproliferative Potential of Celtis iguanaea against Ovarian (OVCAR-3) and Colon (HT-29) Tumor Cell

“…The triterpenes and phytosterols are generally found in abundance in the plants and are structurally resemble to the molecule of cholesterol [17]. These compounds are recognized for their hypolipidemic, antioxidant [18] and antiinflammatory effects [19], as well as, have been highlighted by their anticancer potential [20].…”