A multi-targeting natural compound with growth inhibitory and anti-angiogenic properties re-sensitizes chemotherapy resistant cancer

Abstract

Targeted therapies have become the focus of much of the cancer therapy research conducted in the United States. While these therapies have made vast improvements in the treatment of cancer, their results have been somewhat disappointing due to acquired resistances, high cost, and limited populations of susceptible patients. As a result, targeted therapeutics are often combined with other targeted therapeutics or chemotherapies. Compounds which target more than one cancer related pathway are rare, but have the potential to synergize multiple components of therapeutic cocktails. Natural products, as opposed to targeted therapies, typically interact with multiple cellular targets simultaneously, making them a potential source of synergistic cancer treatments. In this study, a rare natural product, deacetylnemorone, was shown to inhibit cell growth in a broad spectrum of cancer cell lines, selectively induce cell death in melanoma cells, and inhibit angiogenesis and invasion. Combined, these results demonstrate that deacetylnemorone affects multiple cancer-related targets associated with tumor growth, drug resistance, and metastasis. Thus, the multi-targeting natural product, deacetylnemorone, has the potential to enhance the efficacy of current cancer treatments as well as reduce commonly acquired treatment resistance.

Anti-Melanogenesis Activity of 6-O-Isobutyrylbritannilactone from Inula britannica on B16F10 Melanocytes and In Vivo Zebrafish Models

“…Likewise, there are several studies that report melanogenesis is suppressed as tyrosinase activity is inhibited by accelerating the proteasomal degradation of tyrosinase [ 33 , 43 ]. On the other hand, previous studies have shown that natural product (NP) compounds are capable of interacting with multiple cellular targets and targeting multiple signaling pathways, thus highlighting the potential of NP compounds as multi-target agents [ 27 , 44 , 45 , 46 ]. The ERK signaling pathway phosphorylates CREB and subsequently activates MITF to promote TYR, TRP1, and TRP2 transcription.…”

Synergistic Effect of Dietary Betaines on SIRT1-Mediated Apoptosis in Human Oral Squamous Cell Carcinoma Cal 27

“…Age-related diseases, including cancer, result from one or more failures at cellular and molecular levels, making difficult the identification of molecular targets for their prevention and treatment. Cancer prevention is an important theme for healthy aging and the role of the quality of one's diet for cancer prevention is definitely worthy of attention [34][35][36][37][38]. As for oral cancer, regarded as the main cause of death from oral diseases in many countries with the global estimates in 2018 of 354,864 new cases and 177,384 deaths, chemoprevention by dietary agents has evolved as a promising approach to control the incidence which has increased in many countries, especially in younger age groups [39,40].…”

“…As for oral cancer, regarded as the main cause of death from oral diseases in many countries with the global estimates in 2018 of 354,864 new cases and 177,384 deaths, chemoprevention by dietary agents has evolved as a promising approach to control the incidence which has increased in many countries, especially in younger age groups [39,40]. The application of antioxidants or functional foods containing nutrients able to reverse or change epigenetic phenomena, makes nutrition a natural weapon to prevent cancer and improve health span [34][35][36][37][38]. In vitro evaluation of the anticancer effects of lactoferrin and tea polyphenol combination on Cal 27 cells showed a synergistic inhibition with induction of apoptosis and mitochondrial permeability transition [40].…”

Platyphylloside Isolated from Betula platyphylla is Antiproliferative and Induces Apoptosis in Colon Cancer and Leukemic Cells

“…Leukemia treatments include chemotherapy, radiation and targeted therapies, and stem cell transplants. However, the conventional therapies are limited by the associated high costs and anticancer drug toxicity, challenging researchers to develop biocompatible and cost-effective new drugs [5,6,7]. Recent findings have demonstrated the considerable potential of alternative interventions, such as immunotherapy and natural products (NPs), in the treatment of leukemia [5,6,7].…”

“…However, the conventional therapies are limited by the associated high costs and anticancer drug toxicity, challenging researchers to develop biocompatible and cost-effective new drugs [5,6,7]. Recent findings have demonstrated the considerable potential of alternative interventions, such as immunotherapy and natural products (NPs), in the treatment of leukemia [5,6,7]. NPs are capable of targeting multiple cancers and may provide a more robust treatment of cancer by limiting treatment-acquired resistance, increasing the efficacy of individual components in a cancer therapy cocktail, and reducing the associated side-effects to achieve a positive treatment response [5,6,7].…”