Targeting vasculogenic mimicry by phytochemicals: A potential opportunity for cancer therapy

Abstract

Vasculogenic mimicry (VM) is regarded as a process where very aggressive cancer cells generate vascular‐like patterns without the presence of endothelial cells. It is considered as the main mark of malignant cancer and has pivotal role in cancer metastasis and progression in various types of cancers. On the other hand, resistance to the antiangiogenesis therapies leads to the cancer recurrence. Therefore, development of novel chemotherapies and their combinations is urgently needed for abolition of VM structures and also for better tumor therapy. Hence, identifying compounds that target VM structures might be superior therapeutic factors for cancers treatment and controlling the recurrence and metastasis. In recent times, naturally occurring compounds, especially phytochemicals have obtained great attention due to their safe properties. Phytochemicals are also capable of targeting VM structure and also their main signaling pathways. Consequently, in this review article, we illustrated key signaling pathways in VM, and the phytochemicals that affect these structures including curcumin, genistein, lycorine, luteolin, columbamine, triptolide, Paris polyphylla, dehydroeffusol, jatrorrhizine hydrochloride, grape seed proanthocyanidins, resveratrol, isoxanthohumol, dehydrocurvularine, galiellalactone, oxacyclododecindione, brucine, honokiol, ginsenoside Rg3, and norcantharidin. The recognition of these phytochemicals and their safety profile may lead to new therapeutic agents' development for VM elimination in different types of tumors.

Thymoquinone inhibited vasculogenic capacity and promoted mesenchymal-epithelial transition of human breast cancer stem cells

“…Among various types of anaplastic changes, breast cancer remained one of the highest death cases globally [1]. The promotion of pro-angiogenesis signaling as well as VM seems to be an efficient phenomenon in the development of tumor size, metastasis, and invasion to the remote sites [4,5]. Of note, the emergence of CSCs in the tumor niche contributes to resistance against different chemotherapeutic agents such as doxorubicin, etc., leading to high-rate mortality [33][34][35].…”

“…According to previously published data, cells with identical CD24 − / CD44 + markers possess typical CSCs during the progression of breast cancers, leading to poor prognosis [15]. As above-mentioned, breast CSCs like other CSC types could stimulate vascular formation via VM activity [5]. Multiple signaling pathways and effectors such as PI3K, Wnt cascades are closely associated with the VM properties [5,16,17].…”

“…In this regard, the development of de novo blood vessels, so-called angiogenesis, is an efficient way to supply tumor cells' demands [4]. Besides, the expansion of the vascular bed into the tumor mass could facilitate the invasion and metastasis of the remote sites [5]. Angiogenesis is defined as the formation of new blood vessels from the pre-existing vascular network [6][7][8].…”

“…Previous studies have confirmed the existence of vasculogenesis in multiple malignancies, such as ductal breast carcinoma, melanoma, etc. [5].…”

“…As above-mentioned, breast CSCs like other CSC types could stimulate vascular formation via VM activity [5]. Multiple signaling pathways and effectors such as PI3K, Wnt cascades are closely associated with the VM properties [5,16,17]. For instance, it has been shown that PI3K increases VM capacity via the up-regulation of different genes like MT1-MMP and MMP-2, leading to enhanced vasculogenic outcomes [14].…”