Cancer has become a significant concern in the medical sector with increasing disease complexity. Although some available conventional treatments are still a blessing for cancer patients, short-and long-term adverse effects and poor efficiency make it more difficult to treat cancer patients, demonstrating the need for new potent and selective anticancer drugs. In search of potent anticancer agents, naturally occurring compounds have always been admired due to their structural diversity, where Hesperetin (HSP) may be one of the potent candidates. We aimed to summarize all sources, pharmacological properties, anticancer activities of HSP against numerous cancers types through targeting multiple pathological processes, mechanism of HSP on sensitizing the current anti-cancer agents and other phytochemicals, overcoming resistance pattern and determining absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox). Information was retrieved from PubMed, Science Direct, and Google Scholar based on some key points like Hesperetin, cancer name, anticancer resistance, nanoformulation, and ADME/Tox was determined by in silico approaches. HSP is a phytoestrogen present in citrus fruits in a high concentration (several hundred mg/kg) and exhibited anti-cancer activities through interfering at several pathways. HSP can suppress tumor formation by targeting several cellular proteins such as cell cycle regulatory, apoptosis, metastatic, tyrosine kinase, growth factor receptor, estrogen metabolism, and antioxidant-related protein.HSP has shown remarkable synergistic properties in combination therapy and has been reported to overcome multidrug cancer resistance drugs, leading to an improved defensive mechanism. These anticancer activities of HSP may be due to proper structural chemistry. Overall, HSP showed potential anticancer activities against all cancer and possess better pharmacokinetic properties. So this phytochemical alone or combination with other agents can be an effective alternative drug for cancer treatment.

Breast cancer (BC) is one of the most common malignancies in women. Although widespread successful synthetic drugs are available, natural compounds can also be considered as significant anticancer agents for treating BC. Some natural compounds have similar effects as synthetic drugs with fewer side effects on normal cells. Therefore, we aimed to unravel and analyze several molecular mechanisms of genistein (GNT) against BC. GNT is a type of dietary phytoestrogen included in the flavonoid group with a similar structure to estrogen that might provide a strong alternative and complementary medicine to existing chemotherapeutic drugs. Previous research reported that GNT could target the estrogen receptor (ER) human epidermal growth factor receptor-2 (HER2) and several signaling molecules against multiple BC cell lines and sensitize cancer cell lines to this compound when used at an optimal inhibitory concentration. More specifically, GNT mediates the anticancer mechanism through apoptosis induction, arresting the cell cycle, inhibiting angiogenesis and metastasis, mammosphere formation, and targeting and suppressing tumor growth factors. Furthermore, it acts via upregulating tumor suppressor genes and downregulating oncogenes in vitro and animal model studies. In addition, this phytochemical synergistically reverses the resistance mechanism of standard chemotherapeutic drugs, increasing their efficacy against BC. Overall, in this review, we discuss several molecular interactions of GNT with numerous cellular targets in the BC model and show its anticancer activities alone and synergistically. We conclude that GNT can have favorable therapeutic advantages when standard drugs are not available in the pharma markets.

Background: The most common and deadly cancer in female is breast cancer (BC) and new incidence and deaths related to this cancer are rising.Aims: Several issues, that is, high cost, toxicity, allergic reactions, less efficacy, multidrug resistance, and the economic cost of conventional anti‐cancer therapies, has prompted scientists to discover innovative approaches and new chemo‐preventive agents.Materials: Numerous studies are being conducted on plant‐based and dietary phytochemicals to discover new‐fangled and more advanced therapeutic approaches for BC management.Result: We have identified that natural compounds modulated many molecular mechanisms and cellular phenomena, including apoptosis, cell cycle progression, cell proliferation, angiogenesis and metastasis, up‐regulation of tumor‐suppressive genes, and down‐regulation of oncogenes, modulation of hypoxia, mammosphere formation, onco‐inflammation, enzymatic regulation, and epigenetic modifications in BC. We found that a number of signaling networks and their components such as PI3K/Akt/mTOR, MMP‐2 and 9, Wnt/‐catenin, PARP, MAPK, NF‐κB, Caspase‐3/8/9, Bax, Bcl2, Smad4, Notch1, STAT3, Nrf2, and ROS signaling can be regulated in cancer cells by phytochemicals. They induce up‐regulation of tumor inhibitor microRNAs, which have been highlighted as a key player for ani‐BC treatments followed by phytochemical supplementation.Conclusion: Therefore, this collection offers a sound foundation for further investigation into phytochemicals as a potential route for the development of anti‐cancer drugs in treating patients with BC.

Background: “Dimocarpus longan Lour” is a tropical and subtropical evergreen tree species mainly found in China, India, and Thailand; this plant, found naturally in Bangladesh, even locally, is used as “kaviraj” medication for treating different diseases, such as gastrointestinal disorders, wounds, fever, snake bites, menstrual problem, chickenpox, bone fractures, neurological disorders, and reproductive health. Different parts of this plant, especially juice pulp, pericarp, seeds, leaves, and flowers, contain a diverse group of botanical phytocompounds, and nutrient components which are directly related to alleviating numerous diseases. This literature-based review provides the most up-to-date data on the ethnomedicinal usages, phytochemical profiling, and bio-pharmacological effects of D. longan Lour based on published scientific articles. Methodology: A literature-based review was conducted by collecting information from various published papers in reputable journals and cited organizations. ChemDraw, a commercial software package, used to draw the chemical structure of the phytochemicals. Results: Various phytochemicals such as flavonoids, tannins, and polyphenols were collected from the various sections of the plant, and other compounds like vitamins and minerals were also obtained from this plant. As a treating agent, this plant displayed many biologicals activities, such as anti-proliferative, antioxidant, anti-cancer, anti-tyrosinase, radical scavenging activity, anti-inflammatory activity, anti-microbial, activation of osteoblast differentiation, anti-fungal, immunomodulatory, probiotic, anti-aging, anti-diabetic, obesity, neurological issues, and suppressive effect on macrophages cells. Different plant parts have displayed better activity in different disease conditions. Still, the compounds, such as gallic acid, ellagic acid, corilagin acid, quercetin, 4-O-methyl gallic acid, and (-)-epicatechin showed better activity in the biological system. Gallic acid, corilagin, and ellagic acid strongly exhibited anti-cancer activity in the HepG2, A549, and SGC 7901 cancer cell lines. Additionally, 4-O-methyl gallic acid and (-)-epicatechin have displayed outstanding antioxidant activity as well as anti-cancer activity. Conclusion: This plant species can be considered an alternative source of medication for some diseases as it contains a potential group of chemical constituents.

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease associated with remodeling of the pulmonary artery. We previously reported that the Ca ²⁺ ‐sensing receptor (CaSR) is up‐regulated in pulmonary arterial smooth muscle cells (PASMCs) from patients with idiopathic PAH (IPAH) and contributes to enhanced Ca ²⁺ responses and excessive cell proliferation. However, the mechanisms underlying the up‐regulation of CaSR have not yet been elucidated. We herein examined involvement of platelet‐derived growth factor (PDGF) on CaSR expression, Ca ²⁺ responses, and proliferation in PASMCs. The expression of PDGF receptors was higher in PASMCs from patients with IP AH than in PASMCs from normal subjects. In addition, PDGF‐induced activation of PDGF receptors and their downstream molecules [ERK1/2, p38, protein kinase B, and signal transducer and activator of transcription (STAT) 1/3] were sustained longer in PASMCs from patients with IPAH. The PDGF‐induced CaSR up‐regulation was attenuated by small interfering RNA knockdown of PDGF receptors and STAT1/3, and by the treatment with imatinib. In monocrotaline‐induced pulmonary hypertensive rats, the up‐regulation of CaSR was reduced by imatinib. The combination of NPS2143 and imatinib additively inhibited the development of pulmonary hypertension. These results suggest that enhanced PDGF signaling is involved in CaSR up‐regulation, leading to excessive PASMC proliferation and vascular remodeling in patients with IPAH. The linkage between CaSR and PDGF signals is a novel pathophysiological mechanism contributing to the development of PAH.—Yamamura, A., Nayeem, M. J., Al Mamun, A., Takahashi, R., Hayashi, H., Sato, M. Platelet‐derived growth factor up‐regulates Ca ²⁺ ‐sensing receptors in idiopathic pulmonary arterial hypertension. FASEB J. 33, 7363–7374 (2019). www.fasebj.org