Using natural products to promote caspase-8-dependent cancer cell death

Abstract

The selective killing of cancer cells without toxicity to normal nontransformed cells is an idealized goal of cancer therapy. Thus, there has been much interest in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a protein that appears to selectively kill cancer cells. TRAIL has been reported to trigger apoptosis and under some circumstances, an alternate death signaling pathway termed necroptosis. The relative importance of necroptosis for cell death induction in vivo is under intensive investigation. Nonetheless, many cancer cells (particularly those freshly isolated from cancer patients) are highly resistant to TRAIL-mediated cell death. Therefore, there is an underlying interest in identifying agents that can be combined with TRAIL to improve its efficacy. There are numerous reports in which combination of TRAIL with standard antineoplastic drugs has resulted in enhanced cancer cell death in vitro. However, many of these chemotherapeutic drugs are nonspecific and associated with adverse effects, which raise serious concerns for cancer therapy in patients. By contrast, natural products have been shown to be safer and efficacious alternatives. Recently, a number of studies have suggested that certain natural products when combined with TRAIL can enhance cancer cell death. In this review, we highlight molecular pathways that might be targeted by various natural products to promote cell death, and focus on our recent work with withanolides as TRAIL sensitizers. Finally, we will suggest synergistic approaches for combining active withanolides with various forms of immunotherapy to promote cancer cell death and an effective antitumor immune response.

Cell Cycle Arrest in Different Cancer Cell Lines &ldquo;Liver, Breast, and Colon&rdquo; Induce Apoptosis under the Influence of the Chemical Content of <em>Aeluropus lagopoides</em> Leaves Extracts

“…In this point of view, both extracts look to induce apoptotic that may activate via cyclin E or D, R point or one of the chick points that present in G0-G1 phase [24,25]. On the other hand, the qualitative chemical analysis (Table 3) indicates that both hexane and ethyl acetate extracts contain hydrophobic bioactive compounds such as phytosteroid, terpenoids, cardioglycoside and fixed oil, which had confirmed their antiproliferative activity in previous studies [8,26]. In the light of affording mentioned and observed results; the suggested mechanism of action of hydrophobic molecules extracted from A. lagopoides is related to their capability to flow through the phospholipid bilayer membrane of the cell easily, this changes the internal cellular homeostasis, which leads to arrest cell division.…”

In-vitro evaluation of apoptotic effect of OEO and thymol in 2D and 3D cell cultures and the study of their interaction mode with DNA

“…Therefore one of the toxicological mechanisms of OEO/thymol for inhibition of MDA-MB231 is the blockage of DNA replication, resulting in S-phase arrest and ultimately apoptosis. Although, some anticancer drugs initiate cell death through death receptors on the surface of the cell membrane (extrinsic pathway) 57 , most studies suggest a caspase-dependent pathway in mitochondria-based apoptosis (intrinsic pathway) by drugs 58 , 59 . However, the relationship between these paths has been observed at different levels.…”

Manilkara zapota (L.) P. Royen Leaf Water Extract Induces Apoptosis in Human Hepatocellular Carcinoma (HepG2) Cells via ERK1/2/Akt1/JNK1 Signaling Pathways

“…Numerous chemotherapeutic drugs, including doxorubicin [ 34 ], tamoxifen [ 35 ], and cisplatin [ 36 ], inhibit neoplastic cells via cell cycle arrest and apoptosis induction. This suggests that natural products regardless of isolated bioactive compounds or crude extracts must stimulate the signals associated with cell death in order to serve as a potential agent in cancer therapy [ 37 ]. In order to validate Manilkara zapota leaf water extract induced apoptosis in HepG2 cells, Annexin V-FITC and propidium iodide fluorescence staining was measured quantitatively.…”