The quinone-based derivative, HMNQ induces apoptotic and autophagic cell death by modulating reactive oxygen species in cancer cells

Abstract

8-Hydroxy-2-methoxy-1,4-naphthoquinone (HMNQ), a natural compound isolated from the bark of Juglans sinensis Dode, displays cytotoxic activity against various human cancer cells. However, the molecular mechanism of the anticancer effect is unclear. In this study, we examined the cytotoxic mechanism of HMNQ at the molecular level in human cancer cells. Cells were treated with HMNQ in a dose- or time-dependent manner. HMNQ treatment inhibited cell viability, colony formation and cell migration, indicating that HMNQ induced cancer cell death. HMNQ-treated cells resulted in apoptotic cell death through PARP-1 cleavage, Bax upregulation and Bcl-2 downregulation. HMNQ was also observed to induce autophagy by upregulating Beclin-1 and LC3. Furthermore, HMNQ induced reactive oxygen species (ROS) production, which was attenuated by the ROS scavengers, NAC and GSH. Finally, HMNQ increased expression of JNK phosphorylation and the JNK inhibitor SP600125 rescued HMNQ-induced cell death, suggesting that the cytotoxicity of HMNQ is mediated by the JNK signaling pathway. Taken together, our findings show that HMNQ exhibits anticancer activity through induction of ROS-mediated apoptosis and autophagy in human cancer cells. These data suggest the potential value of HMNQ as a natural anticancer drug.

Cytostatic and Anti-tumor Potential of Ajwa Date Pulp against Human Hepatocellular Carcinoma HepG2 Cells

“…ROS has been regarded as an important regulator of both extrinsic and intrinsic pathways of cell survival and cell death 34 . Various natural agents that are used as anticancer compounds can lead to cell death of many cancer cells by causing overproduction of ROS 35 . Flow cytometry analysis of ROS generation confirmed that ADP extract stimulated ROS production in HCC cells by causing oxidative stress, destabilizing mitochondria and consequently induced apoptosis (Fig.…”

Synthesis of Murrayaquinone‐A Derivatives and Investigation of Potential Anticancer Properties

“…Among the therapeutic agents with the quinone ring, the antitumor activity of the carbazole alkaloids is known to be quite high [8] . The quinone or quinone‐derived compounds have been shown to have anticancer activity against a variety of cancer types, such as leukemia, non‐small cell lung cancer, small cell lung cancer, colon cancer, central nervous system cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer [9–12] . In our study, we focused on the synthesis of murryaquinone A – one of the important carbazolequinone alkaloids‐ and its derivatives, as well as the evaluation of their cytotoxic activity on healthy and cancerous colon cell lines.…”

Phytochemicals as a Complement to Cancer Chemotherapy: Pharmacological Modulation of the Autophagy-Apoptosis Pathway

“…Gallic acid additionally encourages apoptosis through ROS-mediated activation of JNK pathways (Chen et al, 2013b). Oxidation of catechin-derived quinone has also been observed to result in anti-tumor activities in several human cancer cells through apoptotic as well as autophagic cell death via modulating ROS (Saibu et al, 2014;Lee et al, 2017). Thus, activation of oxidative stress signaling may not always be associated with unexpected side effects.…”